Yes-associated protein (YAP) activity responded to physical and mechanical cues such as extracellular matrix (ECM), cell density and the mechanical regulation of YAP controlled cellular proliferation and inhibition of apoptotic signals. The intervertebral disc (IVD) comprises a heterogeneous population of cells, including those of the nucleus pulposus (NP) and annulus fibrosus (AF), which are diverse in phenotype, partly due to the different ECM and mechanical loads they experience. How do IVD cells sense microenvironment and what is the relationship between YAP and cytoskeleton in the process of intervertebral disc degeneration (IDD) are not well understood. First, Hippo pathway and cytoskeleton organisation were assessed in the NP and AF of immature (4 weeks), mature (14 weeks), aged (50 weeks), and degenerated (14 weeks, 4 weeks after annulus puncture) IVDs. Second, to assess the effect of ECM composition and cell density on cytoskeleton and YAP levels, we seeded cells at different densities on three types of ECM. In this study, YAP and F-actin activity decreased gradually with age in natural IDD. Hippo signalling was suppressed in the early stages of disc injury, demonstrating the potential for endogenous repair, but this repair did not prevent further disc degeneration. β-tubulin and vimentin filaments provide the cell with its shape and its elastic properties in resisting mechanical forces. The Hippo pathway and cytoskeleton were shown to be regulated by cell density and the ECM composition.

中文翻译：

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河马通路在椎间盘退变期间协调细胞骨架组织。

Yes 相关蛋白 (YAP) 活性对物理和机械信号作出反应，例如细胞外基质 (ECM)、细胞密度和 YAP 的机械调节控制细胞增殖和抑制凋亡信号。椎间盘 (IVD) 包含异质的细胞群，包括髓核 (NP) 和纤维环 (AF) 的细胞群，它们的表型不同，部分原因是它们经历的不同 ECM 和机械负荷。IVD细胞如何感知微环境以及椎间盘退变（IDD）过程中YAP与细胞骨架之间的关系尚不清楚。首先，在未成熟（4 周）、成熟（14 周）、老化（50 周）和退化（14 周，环穿刺后 4 周）IVD。其次，为了评估 ECM 组成和细胞密度对细胞骨架和 YAP 水平的影响，我们在三种类型的 ECM 上接种了不同密度的细胞。在这项研究中，自然 IDD 中 YAP 和 F-肌动蛋白活性随着年龄的增长而逐渐下降。Hippo 信号在椎间盘损伤的早期被抑制，证明了内源性修复的潜力，但这种修复并没有阻止进一步的椎间盘退化。β-微管蛋白和波形蛋白丝为细胞提供了其形状和抵抗机械力的弹性特性。Hippo 通路和细胞骨架显示受细胞密度和 ECM 组成的调节。在这项研究中，自然 IDD 中 YAP 和 F-肌动蛋白活性随着年龄的增长而逐渐下降。Hippo 信号在椎间盘损伤的早期被抑制，证明了内源性修复的潜力，但这种修复并没有阻止进一步的椎间盘退化。β-微管蛋白和波形蛋白丝为细胞提供了其形状和抵抗机械力的弹性特性。Hippo 通路和细胞骨架显示受细胞密度和 ECM 组成的调节。在这项研究中，自然 IDD 中 YAP 和 F-肌动蛋白活性随着年龄的增长而逐渐下降。Hippo 信号在椎间盘损伤的早期被抑制，证明了内源性修复的潜力，但这种修复并没有阻止进一步的椎间盘退化。β-微管蛋白和波形蛋白丝为细胞提供了其形状和抵抗机械力的弹性特性。Hippo 通路和细胞骨架显示受细胞密度和 ECM 组成的调节。β-微管蛋白和波形蛋白丝为细胞提供了其形状和抵抗机械力的弹性特性。Hippo 通路和细胞骨架显示受细胞密度和 ECM 组成的调节。β-微管蛋白和波形蛋白丝为细胞提供了其形状和抵抗机械力的弹性特性。Hippo 通路和细胞骨架显示受细胞密度和 ECM 组成的调节。